General Information of Drug Therapeutic Target (DTT) (ID: TT09EZF)

DTT Name Charged multivesicular body protein 4B (CHMP4B)
Synonyms
hVps322; hVps32-2; hSnf72; hSnf7-2; Vps322; Vps32-2; Vacuolar protein sortingassociated protein 322; Vacuolar protein sorting-associated protein 32-2; SNF72; SNF7-2; SNF7 homolog associated with Alix 1; SHAX1; Chromatinmodifying protein 4b; Chromatin-modifying protein 4b; CHMP4b; C20orf178
Gene Name CHMP4B
DTT Type
Literature-reported target
[1]
UniProt ID
CHM4B_HUMAN
TTD ID
T47731
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSVFGKLFGAGGGKAGKGGPTPQEAIQRLRDTEEMLSKKQEFLEKKIEQELTAAKKHGTK
NKRAALQALKRKKRYEKQLAQIDGTLSTIEFQREALENANTNTEVLKNMGYAAKAMKAAH
DNMDIDKVDELMQDIADQQELAEEISTAISKPVGFGEEFDEDELMAELEELEQEELDKNL
LEISGPETVPLPNVPSIALPSKPAKKKEEEDDDMKELENWAGSM
Function
MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Plays a role in the endosomal sorting pathway. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan. Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs.
KEGG Pathway
Viral life cycle - HIV-1 (hsa03250 )
Endocytosis (hsa04144 )
Necroptosis (hsa04217 )
Reactome Pathway
Macroautophagy (R-HSA-1632852 )
Pyroptosis (R-HSA-5620971 )
Endosomal Sorting Complex Required For Transport (ESCRT) (R-HSA-917729 )
HCMV Late Events (R-HSA-9610379 )
Late endosomal microautophagy (R-HSA-9615710 )
Sealing of the nuclear envelope (NE) by ESCRT-III (R-HSA-9668328 )
Translation of Replicase and Assembly of the Replication Transcription Complex (R-HSA-9679504 )
Translation of Replicase and Assembly of the Replication Transcription Complex (R-HSA-9694676 )
Budding and maturation of HIV virion (R-HSA-162588 )

References

1 High CHMP4B expression is associated with accelerated cell proliferation and resistance to doxorubicin in hepatocellular carcinoma. Tumour Biol. 2015 Apr;36(4):2569-81.